Mete Yeginer

Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

PURPOSE To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. METHODS AND MATERIALS We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving≥10 and 20 Gy (V10 and V20) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. RESULTS In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V10 (regression coefficient (β)=-0.060, p=0.009) and V20 (β=-0.044, p=0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V10 and V20 were as follows: -0.022 (p=0.025) and -0.021 (p=0.002), respectively. Patients with V10≥95% were more likely to experience Grade≥3 leukopenia (68.8% vs. 24.6%, p<0.001) than were patients with V20>76% (57.7% vs. 21.8%, p=0.001). CONCLUSIONS These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V10<95% and V20<76% may reduce HT.

TOTAL MARROW IRRADIATION WITH RAPIDARC VOLUMETRIC ARC THERAPY

PURPOSE To develop a volumetric arc therapy (VMAT)-total marrow irradiation (TMI) technique for patients with hematologic malignancies. METHODS AND MATERIALS VMAT planning was performed for 6 patients using RapidArc technology. The planning target volume consisted of all the bones in the body from the head to the mid-femur, excluding the extremities, except for the humerus, plus a 3.0-mm margin. The organs at risk included the lungs, heart, liver, kidneys, bowels, brain, eyes, and oral cavity. The VMAT-TMI technique consisted of three plans: the head and neck, the chest, and the pelvis, each with three 330° arcs. The plans were prescribed to ensure, at a minimum, 95% planning target volume dose coverage with the prescription dose (percentage of volume receiving dose of ≥12 Gy was 95%). The treatments were delivered and verified using MapCheck and ion chamber measurements. RESULTS The VMAT-TMI technique reported in the present study provided comparable dose distributions with respect to the fixed gantry linear accelerator intensity-modulated TMI. RapidArc planning was less subjective and easier, and, most importantly, the delivery was more efficient. RapidArc reduced the treatment delivery time to approximately 18 min from 45 min with the fixed gantry linear accelerator intensity-modulated TMI. When the prescription dose coverage was reduced to 85% from 95% and the mandible and maxillary structures were not included in the planning target volume as reported in a tomotherapy study, a considerable organ at risk dose reduction of 4.2-51% was observed. The average median dose for the lungs and lenses was reduced to 5.6 Gy from 7.2 Gy and 2.4 Gy from 4.5 Gy, respectively. CONCLUSION The RapidArc VMAT technique improved the treatment planning, dose conformality, and, most importantly, treatment delivery efficiency. The results from our study suggest that the RapidArc VMAT technology can be expected to facilitate the clinical transition of TMI.

Verification of dose distribution for volumetric modulated arc therapy total marrow irradiation in a humanlike phantom.

PURPOSE Volumetric modulated arc therapy (VMAT) treatment planning studies have been reported to provide good target coverage and organs at risk (OARs) sparing in total marrow irradiation (TMI). A comprehensive dosimetric study simulating the clinical situation as close as possible is a norm in radiotherapy before a technique can be used to treat a patient. Without such a study, it would be difficult to make a reliable and safe clinical transition especially with a technique as complicated as VMAT-TMI. To this end, the dosimetric feasibility of VMAT-TMI technique in terms of treatment planning, delivery efficiency, and the most importantly three dimensional dose distribution accuracy was investigated in this study. The VMAT-TMI dose distribution inside a humanlike Rando phantom was measured and compared to the dose calculated using RapidArc especially in the field junctions and the inhomogeneous tissues including the lungs, which is the dose-limiting organ in TMI. METHODS Three subplans with a total of nine arcs were used to treat the planning target volume (PTV), which was determined as all the bones plus the 3 mm margin. Thermoluminescent detectors (TLDs) were placed at 39 positions throughout the phantom. The measured TLD doses were compared to the calculated plan doses. Planar dose for each arc was verified using mapcheck. RESULTS TLD readings demonstrated accurate dose delivery, with a median dose difference of 0.5% (range: -4.3% and 6.6%) from the calculated dose in the junctions and in the inhomogeneous medium including the lungs. CONCLUSIONS The results from this study suggest that RapidArc VMAT technique is dosimetrically accurate, safe, and efficient in delivering TMI within clinically acceptable time frame.

LINEAR ACCELERATOR-BASED INTENSITY-MODULATED TOTAL MARROW IRRADIATION TECHNIQUE FOR TREATMENT OF HEMATOLOGIC MALIGNANCIES: A DOSIMETRIC FEASIBILITY STUDY

PURPOSE To investigate the dosimetric feasibility of linear accelerator-based intensity-modulated total marrow irradiation (IM-TMI) in patients with hematologic malignancies. METHODS AND MATERIALS Linear accelerator-based IM-TMI treatment planning was performed for 9 patients using the Eclipse treatment planning system. The planning target volume (PTV) consisted of all the bones in the body from the head to the mid-femur, except for the forearms and hands. Organs at risk (OAR) to be spared included the lungs, heart, liver, kidneys, brain, eyes, oral cavity, and bowel and were contoured by a physician on the axial computed tomography images. The three-isocenter technique previously developed by our group was used for treatment planning. We developed and used a common dose-volume objective method to reduce the planning time and planner subjectivity in the treatment planning process. RESULTS A 95% PTV coverage with the 99% of the prescribed dose of 12 Gy was achieved for all nine patients. The average dose reduction in OAR ranged from 19% for the lungs to 68% for the lenses. The common dose-volume objective method decreased the planning time by an average of 35% and reduced the inter- and intra- planner subjectivity. CONCLUSION The results from the present study suggest that the linear accelerator-based IM-TMI technique is clinically feasible. We have demonstrated that linear accelerator-based IM-TMI plans with good PTV coverage and improved OAR sparing can be obtained within a clinically reasonable time using the common dose-volume objective method proposed in the present study.

WE-C-BRB-03: Feasibility Study for Total Marrow Irradiation with RapidArc Volumetric Arc Therapy (VMAT-TMI)

Purpose: To investigate the dosimetric feasibility of VMAT‐TMI technique in terms of treatment planning and delivery efficiency and accuracy for a Rando phantom using Eclipse RapidArc technology. Methods: Total body irradiation (TBI) has been an integral part of pre‐conditioning regimens for the treatment of hematologic malignancies. Normal tissue toxicity is a common complication of TBI inclusive regimens especially at doses higher than 12 Gy due to inhomogeneous and excessive dose to organs at risk (OARs). Fixed gantry linear accelerator(linac) and Tomotherapy intensity modulated total bone marrow (IM‐TMI) techniques have been reported to reduce doses to OARs. However, the treatment time of more than one hour with both techniques may limit their clinical application. Volumetric modulated arc therapy (VMAT) may be able to increase the treatmentdelivery efficiency while increasing the target conformality and reducing the radiationdose to OARs. In order to treat all the bones in the Rando phantom, three sub‐plans with a total of nine arcs were used. A total of 100 thermoluminescent detectors(TLDs) were placed at 39 positions throughout the phantom. The measured TLDdoses were compared to the calculated plan doses. Planar dose for each arc was verified using MapCheck and MapPhan. Results: Excellent target coverage with the prescription dose and dose reduction to the OARs were achieved similar to the fixed gantry linac IM‐TMI technique. The number of monitor units was decreased by 50%, while the delivery efficiency increased by more than 60%. TLD readings demonstrated accurate dosedelivery, with a median dose difference of 0.5% from the calculated dose. Planar dose distributions of all arcs satisfied the 3% and 3 mm gamma criteria with an average pass rate of 97.8%. Conclusions: Results from this study suggest that RapidArc VMAT‐TMI technique is clinically feasible. This study is supported by Varian Medical Systems

SU‐GG‐T‐565: Radiotherapy of Patients with Bilateral Hip Replacement Using Volumetric Modulated Arc Therapy (RapidArc)

Purpose: To investigate a volumetric modulated arc therapy (RapidArc)‐based scheme to improve dose homogeneity, target coverage and organ at risk sparing in prostate cancer patients with hip replacement. Method and Materials: RapidArc (RA) treatment plans for previously treated 7 prostate patients with hip replacement are generated and compared with the IMRT plans used in their treatments. The total prescription dose of 50.4 Gy is delivered in 28 fractions of 1.8 Gy/fraction. Organs at risk (OARs) include bladder, rectum, small bowel and femoral heads. Magnetic Resonanceimages are co‐registered with computed tomographyimages to correctly delineate prostate volume. Inhomogeneity correction is turned off for both IMRT and RA plans. Single (sRA) and double (dRA) RapidArc plans are generated and compared with the seven‐field IMRT plans. Two 60‐degree lateral sectors between 60–120 degrees and 240–300 degrees were skipped to avoid irradiation through the high Z materials in the hip. All plans are optimized and normalized to provide a minimum of 94% target coverage with the prescription dose.Results: The maximum PTV doses are 54.5Gy (IMRT), 57.1Gy (sRA) and 52.8Gy (dRA). Overall, dRA performed better in PTV coverage, dose homogeneity and the OAR sparing than did sRA and IMRT. For instance, V100 for rectum is 13%, 30% and 50% with dRA, IMRT and sRA. Homogeneity index (HI) is 103.5%, 106.7% and 109% for dRA, IMRT and sRA, respectively. The total monitor unit is 968 MU (IMRT), 429 MU (sRA ) and 518 MU (dRA). Conclusion: RapidArc with one and two arcs is investigated in prostate cancer patients with hip replacement. Only RapidArc with two arcs (dRA) showed some improvements in OAR and healthy tissue sparing, target coverage and dose homogeneity with respect to IMRT. The treatment delivery is more efficient with single arc RapidArc. Conflict of Interest: Sponsored by Varian Medical Systems, Inc.

SU‐GG‐T‐106: Simultaneous Integrated Boost Radiotherapy Using Volumetric Modulated Arc Therapy (RapidArc) in the Treatment of Head&Neck Cancer: A Dosi metric Comparison with Helical TomoTherapy and Intensity Modulated Radiotherapy

Purpose: To evaluate the treatment planning performance of volumetric modulated arc therapy (RapidArc) in patients with head and neck (HN the average minimum PTV70 doses were (97.9±1.0)%, (98.1±0.3)% and (96.7±1.9)%. The maximum and mean OAR doses for parotid glands, mandible and larynx were comparable while statistically significant differences were observed in the brainstem, spinal cord and esophagus. The average mean doses to brainstem, for instance, were 7±2.6 Gy (IMRT), 11.8±5.1 Gy (RA) and 20.2±6.3 Gy (HT). Conclusion:IMRT performed better in dose sparing for brainstem, spinal cord, and esophagus than did RapidArc and Tomotherapy when delivering SIB in patients with H&N cancer. Tomotherapy was found to provide the highest PTV dose homogeneity while the treatment delivery was more efficient with RA. Conflict of Interest: Research sponsored by Varian Medical Systems, Inc.